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The Structure of the Cyprinid herpesvirus 3 ORF112-Z?·Z-DNA Complex Reveals a Mechanism of Nucleic Acids Recognition Conserved with E3L, a Poxvirus Inhibitor of Interferon Response.


ABSTRACT: In vertebrate species, the innate immune system down-regulates protein translation in response to viral infection through the action of the double-stranded RNA (dsRNA)-activated protein kinase (PKR). In some teleost species another protein kinase, Z-DNA-dependent protein kinase (PKZ), plays a similar role but instead of dsRNA binding domains, PKZ has Z? domains. These domains recognize the left-handed conformer of dsDNA and dsRNA known as Z-DNA/Z-RNA. Cyprinid herpesvirus 3 infects common and koi carp, which have PKZ, and encodes the ORF112 protein that itself bears a Z? domain, a putative competitive inhibitor of PKZ. Here we present the crystal structure of ORF112-Z? in complex with an 18-bp CpG DNA repeat, at 1.5 Å. We demonstrate that the bound DNA is in the left-handed conformation and identify key interactions for the specificity of ORF112. Localization of ORF112 protein in stress granules induced in Cyprinid herpesvirus 3-infected fish cells suggests a functional behavior similar to that of Z? domains of the interferon-regulated, nucleic acid surveillance proteins ADAR1 and DAI.

SUBMITTER: Kus K 

PROVIDER: S-EPMC4692202 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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The Structure of the Cyprinid herpesvirus 3 ORF112-Zα·Z-DNA Complex Reveals a Mechanism of Nucleic Acids Recognition Conserved with E3L, a Poxvirus Inhibitor of Interferon Response.

Kuś Krzysztof K   Rakus Krzysztof K   Boutier Maxime M   Tsigkri Theokliti T   Gabriel Luisa L   Vanderplasschen Alain A   Athanasiadis Alekos A  

The Journal of biological chemistry 20151111 52


In vertebrate species, the innate immune system down-regulates protein translation in response to viral infection through the action of the double-stranded RNA (dsRNA)-activated protein kinase (PKR). In some teleost species another protein kinase, Z-DNA-dependent protein kinase (PKZ), plays a similar role but instead of dsRNA binding domains, PKZ has Zα domains. These domains recognize the left-handed conformer of dsDNA and dsRNA known as Z-DNA/Z-RNA. Cyprinid herpesvirus 3 infects common and ko  ...[more]

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